DESCRIPTION (Verbatim from Applicant's Abstract): Cardiovascular disease is the leading cause of death in the United States. Techniques to address this problem such as laser angioplasty showed promise early on, but enthusiasm waned in the face of inadvertent vascular perforation, restenosis, and thrombosis. The overall objective of the proposed research is to develop and test a new class of broadband endoscopic and catheter based systems for the diagnosis and therapy of cardiovascular disease. This new generation of catheter based devices is designed to overcome the problems associated with laser angioplasty and extend the frequency range of IR which can be administered. We also propose to develop, for the first time, multiple energy catheters that will permit simultaneous imaging with JR and ultrasound (U/S). Simultaneous, multi-energy images may permit a more accurate assessment of vascular plaque type. The proposed imaging systems will be forward-Jooking rather than side-looking unlike all conventional intravascular ultrasound scanners. To address the overall objective we propose the following specific aims: 1) measure IR absorbance spectra of various atherosclerotic plaque (in vitro and in vivo) in the 2 to 10 um range, 2) perform tissue-specific, evanescent optical wave ablation of atherosclerotic plaque (in vitro and in vivo) at wavelengths determined from aim 1, using the continuously tunable IR free-electron laser (FEL) at Duke University, 3) design, construct, and test a broadband multi-energy catheter that permits simultaneous forward-looking JR and U/S imaging, and 4) design, construct, and test a broadband multi-energy catheter that permits sequential JR imaging and ablation. Perhaps the most profound advantage of this approach is the combined use of evanescent waves and multiple energy endoscopic delivery for precise, controlled laser surgery and diagnosis in a minimally invasive setting. The program will evolve from benchtop experiments using the JR FEL to advanced fiber optics that incorporate specialized optical micro-electro-mechanical systems (MEMS) sources and sensors for diagnostic and therapeutic devices. Results from aims 1 and 2 will guide the construction phase of the advanced MEMS source and detection arrays. The integration of MEMS and smart pixel arrays has the potential of making available to cardiovascular medicine high performance, inexpensive and unique catheters. Such catheters could have a major impact on the treatment of cardiovascular disease and may find application in other disease entities.